Extracellular vesicles of human glial cells exert neuroprotective effects via brain miRNA modulation in a rat model of traumatic brain injury.

Autor: Salikhova DI; Institute of Molecular and Cellular Medicine, Medical Institute, RUDN University, Moscow, Russian Federation, 117198. diana_salikhova@bk.ru.; Research Centre for Medical Genetics, Moscow, Russian Federation, 115522. diana_salikhova@bk.ru., Timofeeva AV; V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow, Russian Federation, 117997., Golovicheva VV; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russian Federation, 119992., Fatkhudinov TK; Institute of Molecular and Cellular Medicine, Medical Institute, RUDN University, Moscow, Russian Federation, 117198.; Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution 'Petrovsky National Research Centre of Surgery', Moscow, Russian Federation, 117418., Shevtsova YA; V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow, Russian Federation, 117997.; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russian Federation, 119234., Soboleva AG; Institute of Molecular and Cellular Medicine, Medical Institute, RUDN University, Moscow, Russian Federation, 117198.; Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution 'Petrovsky National Research Centre of Surgery', Moscow, Russian Federation, 117418., Fedorov IS; V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow, Russian Federation, 117997., Goryunov KV; V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow, Russian Federation, 117997., Dyakonov AS; Research Centre for Medical Genetics, Moscow, Russian Federation, 115522., Mokrousova VO; Research Centre for Medical Genetics, Moscow, Russian Federation, 115522., Shedenkova MO; Institute of Molecular and Cellular Medicine, Medical Institute, RUDN University, Moscow, Russian Federation, 117198.; Research Centre for Medical Genetics, Moscow, Russian Federation, 115522., Elchaninov AV; Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution 'Petrovsky National Research Centre of Surgery', Moscow, Russian Federation, 117418., Makhnach OV; Research Centre for Medical Genetics, Moscow, Russian Federation, 115522., Kutsev SI; Research Centre for Medical Genetics, Moscow, Russian Federation, 115522., Chekhonin VP; The Serbsky State Scientific Center for Social and Forensic Psychiatry, Moscow, Russian Federation, 119034., Silachev DN; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russian Federation, 119992. silachevdn@belozersky.msu.ru., Goldshtein DV; Institute of Molecular and Cellular Medicine, Medical Institute, RUDN University, Moscow, Russian Federation, 117198.; Research Centre for Medical Genetics, Moscow, Russian Federation, 115522.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Nov 21; Vol. 13 (1), pp. 20388. Date of Electronic Publication: 2023 Nov 21.
DOI: 10.1038/s41598-023-47627-2
Abstrakt: Stem cell-based therapeutic approaches for neurological disorders are widely studied. Paracrine factors secreted by stem cells in vitro and delivered intranasally might allow bypassing the disadvantages associated with a surgical cell delivery procedure with likely immune rejection of a transplant. In this study, we investigated the therapeutic effect of the extracellular vesicles secreted by glial progenitor cells (GPC-EV) derived from human induced pluripotent stem cell in a traumatic brain injury model. Intranasal administration of GPC-EV to Wistar rats for 6 days improved sensorimotor functions assessed over a 14-day observation period. Beside, deep sequencing of microRNA transcriptome of GPC-EV was estimate, and was revealed 203 microRNA species that might be implicated in prevention of various brain pathologies. Modulation of microRNA pools might contribute to the observed decrease in the number of astrocytes that inhibit neurorecovery processes while enhancing neuroplasticity by decreasing phosphorylated Tau forms, preventing inflammation and apoptosis associated with secondary damage to brain tissue. The course of GPC-EV administration was promoted the increasing protein levels of NF-κB in studied areas of the rat brain, indicating NF-κB dependent mechanisms as a plausible route of neuroprotection within the damaged area. This investigation showed that GPC-EV may be representing a therapeutic approach in traumatic brain injury, though its translation into the clinic would require an additional research and development.
(© 2023. The Author(s).)
Databáze: MEDLINE
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